PATIENT INFORMATION LEAFLET

Herceptin 150mg powder for concentrate for solution for infusion

trastuzumab

Read this leaflet carefully before you start using this medicine, because

it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Herceptin contains trastuzumab as its active substance, which is a monoclonal antibody. Monoclonal antibodies specifically recognize proteins or antigens. Trastuzumab is designed to selectively bind to an antigen called the human epidermal growth factor receptor 2 (HER2). The HER2 is found in large quantities on the surface of some cancer cells and stimulates the growth of these cells. When Herceptin binds to HER2, it slows down the growth of these cells, causing them to die.

Your doctor may prescribe Herceptin for the treatment of breast or stomach cancer when:

• you have early-stage breast cancer with high levels of a protein called HER2.
• you have metastatic breast cancer (breast cancer in which the original tumor has spread) with high levels of HER2. Herceptin may be prescribed in combination with chemotherapy medications paclitaxel or docetaxel as a first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have not been successful. It is also used in combination with other medications called aromatase inhibitors in patients with high levels of HER2 and hormone receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex hormones).
• you have metastatic stomach cancer with high levels of HER2, and it is combined with other cancer medications such as capecitabina or 5-fluorouracilo and cisplatino.

No use Herceptin:

• If you are allergic to trastuzumab, mouse proteins, or any of the other

components of this medication (listed in section 6).

• If you have severe respiratory problems at rest due to your tumor or if you need oxygen treatment.

Warnings and precautions

Your doctor will closely monitor your treatment.

Cardiac reviews

Treatment with Herceptin alone or in combination with a taxane may affect the heart, especially if you have ever received an anthracycline (taxanes and anthracyclines are two types of medications used to treat cancer). The effects can be moderate to severe and may be fatal. Therefore, you should review your cardiac function before, during (every three months), and after (up to two to five years) treatment with Herceptin. If you develop any signs of heart failure, (inadequate blood pumping by the heart), your doctor will check how your heart functions more frequently (every six to eight weeks), you may receive treatment for heart failure or you may need to interrupt treatment with Herceptin.

Consult your doctor, pharmacist, or nurse before receiving Herceptin if:

• You have had heart failure, coronary artery disease, heart valve disease (heart murmur) or high blood pressure, have taken any medication for high blood pressure or are currently taking any medication for high blood pressure.

• You have ever received or are currently receiving a medication called doxorubicin or epirubicin (cancer medications). These medications (or any other anthracyclines) may damage the heart muscle and increase the risk of heart problems when treated with Herceptin.

• You feel short of breath, especially if you are currently receiving a taxane. Herceptin may cause difficulty breathing, especially when administered for the first time. This could be more severe if you already have shortness of breath. In very rare cases, patients with severe respiratory difficulties before treatment have died when Herceptin was administered.

• You have had any other cancer treatment.

If you receive Herceptin with any other medication to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the prospectuses for these medications.

Children and adolescents

Herceptin is not recommended for individuals under 18 years old.

Other medications and Herceptin

Use of Herceptin with other medications: Inform your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medication.

It may take up to 7 months for Herceptin to be completely eliminated from the body. Therefore, if you are to take any new medication within 7 months of completing treatment, you should inform your doctor, pharmacist, or nurse that you have been treated with Herceptin.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor, pharmacist, or nurse before using this medication.

• You should use an effective contraceptive method during treatment with Herceptin and for at least 7 months after completing treatment.

• Your doctor will explain the risks and benefits of taking Herceptin during pregnancy. In rare cases, a decrease in the fluid surrounding the developing fetus in the womb (amniotic fluid) has been observed in pregnant women who received Herceptin. This may be harmful to the fetus and has been associated with underdeveloped lungs resulting in fetal death.

Breastfeeding

You should not breastfeed your baby during Herceptin therapy and for up to 7 months after the last dose of Herceptin as Herceptin may reach your baby through breast milk.

Consult your doctor or pharmacist before taking a medication.

Driving and operating machinery

Herceptin may affect your ability to drive a vehicle or operate machinery. If you experience symptoms during treatment, such as dizziness, drowsiness, chills, or fever, you should not drive or use machinery until these symptoms disappear.

Before starting treatment with Herceptin, your doctor will determine the amount of HER2 in your tumor. Only patients with a large amount of HER2 will be treated with Herceptin. Herceptin must be administered only by a doctor or nurse. Your doctor will prescribe an appropriate dose and treatment regimen foryou. The dose of Herceptin depends on your body weight.

There are two different types (formulations) of Herceptin:

It is essential to review the medication labeling to ensure that the correct formulation is being administered as prescribed. The intravenous formulation of Herceptin is not for subcutaneous administration and must only be administered intravenously.

Your doctor may consider switching your treatment from intravenous Herceptin to subcutaneous Herceptin (or vice versa) if deemed appropriate for you.

The intravenous formulation of Herceptin is administered as an intravenous infusion (“drip”) directly into a vein. The first dose of your treatment is administered over 90 minutes, and you will be monitored by a healthcare professional while receiving it, in case any adverse reactions occur. If the initial dose is well tolerated, subsequent doses may be administered in 30 minutes (see section 2 “Warnings and precautions”). The number of infusions you can receive will depend on your response to treatment. Your doctor will inform you about this.

To avoid medication errors, it is essential to check the labels on the vials to ensure that the medication being prepared and administered is Herceptin (trastuzumab) and notanother product containing trastuzumab (e.g.trastuzumab emtansine or trastuzumab deruxtecan).

For early-stage breast cancer, metastatic breast cancer, and metastatic gastric cancer, Herceptin will be administered every 3 weeks. Herceptin can also be administered once a week for metastatic breast cancer.

If you interrupt treatment with Herceptin

Do not stop treatment with this medication without first speaking with your doctor. All doses must be taken at the correct time, either weekly or every 3 weeks (depending on your dosing schedule). This helps your medication work effectively.

It may take up to 7 months for Herceptin to be eliminated from your body. Therefore, your doctor may decide to continue monitoring your heart function even after completing your

treatment.

If you have any other questions about using this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, Herceptin can cause side effects, although not everyone will experience them. Some of these side effects can be severe and require hospitalization.

During the administration of a Herceptin infusion, you may experience chills, fever, and other symptoms similar to the flu. This is very common (it can affect more than 1 in 10 people). Other symptoms related to the infusion are: feeling unwell (nausea), vomiting, pain, muscle tension, agitation, headache, dizziness, difficulty breathing, changes in blood pressure, heart rhythm changes (palpitations, arrhythmias, or irregular heartbeat), facial and lip swelling, rash, and feeling tired. Some of these symptoms can be severe and some patients have died (see section 2 "Warnings and precautions").

These side effects mainly occur during the first intravenous infusion ("drip" in vein) and during the first hours after the start of the infusion. They are usually temporary. A healthcare professional will monitor you during the infusion and, for at least six hours, after the start of the first infusion and during two hours after the start of the rest of the infusions. If you have any reaction, they may be able to administer the infusion more slowly or stop the infusion and give you treatment to counteract the side effects. The infusion can continue once your symptoms have improved.

Occasionally, symptoms start after 6 hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms can improve and worsen later.

Severe side effects

Other side effects can occur at any time during treatment with Herceptin and are not related to the infusion.Inform your doctor or nurse if you experience any of the following side effects:

• At times, heart problems can occur during treatment and occasionally after stopping treatment, and these can be severe. These include heart muscle weakness that may cause heart failure, inflammation of the heart layer, and heart rhythm changes. This can cause symptoms such as shortness of breath (even at night), cough, fluid retention (swelling) in the legs or arms, palpitations (arrhythmias or irregular heartbeat) (see section 2. Cardiac reviews).

Your doctor will monitor your heart periodically during and after treatment, but you should inform your doctor immediately if you notice any of the symptoms described above.

• Tumor lysis syndrome (a group of metabolic complications that occur after cancer treatment and are characterized by high levels of potassium and phosphate in the blood and low levels of calcium in the blood). Symptoms can include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (palpitations or irregular heartbeat). Seizures, vomiting, diarrhea, and numbness in the mouth, hands, or feet.

If you experience any of these symptoms after your treatment with Herceptin has ended, consult your doctor and inform them that you were previously treated with Herceptin.

Very common side effects of Herceptin:can affect more than 1 in 10 people:

Common side effects of Herceptin:can affect up to 1 in 10 people:

Rare side effects of Herceptin:can affect up to 1 in 100 people:

Very rare side effects of Herceptin:can affect up to 1 in 1,000 people:

• jaundice
• anaphylactic reactions

Other side effects reported with the use of Herceptin:could not be estimated from the available data:

abnormal blood clotting or coagulation insufficiency

high potassium levels

inflammation or hemorrhages in the back of the eyes

shock

abnormal heart rhythm

difficulty breathing

respiratory insufficiency

acute fluid accumulation in the lungs

acute narrowing of the airways

abnormally low oxygen levels in the blood

difficulty breathing while lying down

liver damage

inflammation of the face, lips, and throat

renal failure

abnormally low fluid levels surrounding the fetus in the womb

lung failure in the fetus

abnormal kidney development in the fetus

Some of the side effects you may experience may be due to your cancer. If you are given Herceptin in combination with chemotherapy, some of the side effects may also be due to the chemotherapy itself.

If you experience side effects, inform your doctor, pharmacist, or nurse.

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through thenational reporting system included in the6HAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Herceptin will be stored by healthcare professionals in the hospital or clinic.

• Keep this medication out of reach of children and pets.

• Do not use this medication after the expiration date that appears on the box and the vial label after EXP.The expiration date is the last day of the month indicated.

• Sealed vials must be stored in a refrigerator (between 2°C and 8°C).

• Do not freeze the reconstituted solution.

• Infusion solutions must be used immediately after dilution. If not used immediately, the storage time until use and the conditions of storage before use will be the responsibility of the user, and in general, should not exceed 24 hours between 2°C and 8°C.

• Do not use this medication if you observe any foreign particles or discoloration before administration.

• Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of empty containers and unused medications. This will help protect the environment.

Composition of Herceptin

• The active ingredient is trastuzumab. Each vial contains 150 mg of trastuzumab that dissolves in 7.2 ml of water for injectable preparations. The resulting solution contains approximately 21 mg/ml of trastuzumab.

• The other components are L-histidine hydrochloride monohydrate, L-histidine, α,α-trehalose dihydrate, polisorbate 20.

Appearance of the product and contents of the pack

Herceptin is a lyophilized powder for concentrate for solution for intravenous infusion, presented in a glass vial with a rubber stopper that contains 150 mg of trastuzumab. It is a white to pale yellow pellet powder. Each pack contains 1 vial of powder.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Responsible for manufacturing

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:7Hhttp://www.ema.europa.eu/

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

This information is intended solely for healthcare professionals:

Herceptin IV is provided in sterile, non-pyrogenic, non-preserved, and single-use vials.

To avoid medication errors, it is essential to check the labels on the vials to ensure that the medication being prepared and administered is Herceptin (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

Always keep this medicine in its original closed container at a temperature of 2°C-8°C in a refrigerator.

Use appropriate aseptic techniques for the reconstitution and dilution procedures. Ensure the sterility of the prepared solutions. Since the medicine does not contain antimicrobial preservatives or bacteriostatic agents, use aseptic techniques.

The reconstituted Herceptin vial with sterile water for injectable preparations (not supplied) is chemically and physically stable for 48 hours at 2°C-8°C after reconstitution and should not be frozen.

After aseptic dilution in 250ml bags of chlorinated polyvinyl chloride, polyethylene, or polypropylene containing 0.9% sodium chloride solution, the physical and chemical stability of Herceptin has been demonstrated for a period of up to 30 days at 2°C-8°C and 24 hours at a temperature not exceeding 30°C.

From a microbiological point of view, the reconstituted solution and the Herceptin infusion solution should be used immediately. If not used immediately, the storage time until use and the conditions of such storage before use will be the responsibility of the user and, in general, should not be more than 24 hours between 2°C and 8°C, unless reconstitution and dilution take place under controlled and validated aseptic conditions.

Storage, handling, and aseptic preparation:

Aseptic handling should be ensured when preparing the infusion. The preparation should be:

• developed under aseptic conditions by qualified personnel in accordance with good practices, especially regarding the aseptic preparation of parenteral products.
• prepared in a laminar flow cabinet or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by proper storage of the prepared infusion solution to ensure maintenance of aseptic conditions.

Each vial of Herceptin should be reconstituted with 7.2ml of water for injectable preparations (not supplied). Avoid using other solvents for reconstitution. This produces a 7.4ml single-dose solution containing approximately 21mg/ml of trastuzumab. A 4% volume overload allows the 150mg dose reflected on the label to be extracted from each vial.

Handle Herceptin carefully during reconstitution. If excessive foam forms during reconstitution or the reconstituted Herceptin is agitated, it may cause problems with the amount of Herceptin that can be extracted from the vial.

Aseptic reconstitution instructions:

1) Using a sterile syringe, slowly inject 7.2ml of water for injectable preparations into the vial containing the Herceptin lyophilisate, directing the flow towards the lyophilisate.

2) Gently move the vial in a circular motion to help reconstitution. DO NOT SHAKE!

The formation of a slight foam after reconstitution is usual. Leave the vial at rest for approximately 5 minutes. The reconstituted Herceptin is a transparent, colorless to pale yellow solution and should be essentially free of visible particles.

Aseptic dilution instructions for the reconstituted solution:

Determine the required solution volume:

• based on the initial dose of 4mg of trastuzumab/kg of body weight or subsequent weekly doses of 2mg of trastuzumab/kg of body weight:

Volume(ml) =Body weight(kg) xDose(4mg/kg initial dose or2mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

• Determine the required solution volume based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8mg/kg initial dose or 6mg/kg for subsequent doses)

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every three weeks of 6mg of trastuzumab/kg of body weight

Volume(ml) =Body weight(kg) xDose(8